Synapsin III Controls Early Phases of Dopaminergic Neurons Development in Fishes and Mammals by Acting Upstream of BDNF and Cdk5 Signaling

Polymorphisms in the Synapsin III (Syn III) gene can associate with attention deficits and hyperactivity disorder (ADHD), a neurodevelopmental characterized by alterations mesocorticolimbic nigrostriatal dopaminergic pathways. In spite of evidence supporting that Syn controls development cortical hippocampal short-projecting neurons, whether it plays similar role midbrain neurons (mDN), owning extensively arborized long-distance multisynaptic axonal projections, was unexplored.Our studies on mDN zebrafish embryos exposed to knock-down (KD), knock-out (ko) mice III-deleted human induced pluripotent stem cells (iPSCs)-derived disclose governs early developmental stages fishes mammals. Differently what observed this occurs through upstream control brain derived neurotrophic factor (BDNF)-mediated cAMP-dependent protein kinase 5 (Cdk5)-stimulated dendrite development. These findings have significant implications for deciphering basis ADHD.